Peo coating on mg screws

ABSTRACT

The present invention relates generally to a bio-degradable implant based on magnesium having a reduced corrosion rate and to a method for the production of such an implant. It is a a method for treating a surface of a bio-degradable metallic implant comprising the following steps: providing a dispersed system comprising a colloid-dispersed apatite and adding an apatite powder to the dispersed system, subjecting an implant to the dispersed system such that a surface of the implant which is to be treated is immersed in the dispersed system wherein the implant comprises a magnesium based alloy, applying an AC voltage difference between the implant as a first electrode and a second electrode positioned in the dispersed system for generating a plasma electrolytic oxidation on the immersed surface of the implant so that the immersed surface is converted to an oxide film which is at least partially covered by apatites formed by the colloid-dispersed apatite and the apatite powder. The evolution of corrosion induced hydrogen gas evolution is decreased and osseointegration is improved.

RELATED APPLICATION

This application claims benefit of and priority to U.S. ProvisionalApplication No. 61/364,970 filed Jul. 16, 2010, the content of which isincorporated herein in its entirety.

FIELD OF THE INVENTION

The present invention relates generally to a bio-degradable implantbased on magnesium having a reduced degradation rate and to a method forthe production of such an implant.

BACKGROUND OF THE INVENTION

It is known that magnesium based alloys posses a number of advantagesthat make them of interest when considering for instance surgicalimplants. Of particular interest of such magnesium based implants is thepossibility of using them to act both as a scaffolding structure onwhich new bone or tissue can grow and as a fixture structure to holdtogether a bone or a ligament long enough to allow natural healing totake place.

Magnesium and its alloys are of particular interest in this type ofapplications as they are bio-compatible and as they have a modulus ofelasticity closer to bone than currently used materials. Another majoradvantage of using magnesium and its alloys as implant materials, forinstance for the fabrication of surgical implants, are their ability tobio-degrade in situ. This in turn means that the implant does not remainin the body. A further surgery to remove the implant is not required.

However, recent animal implantation studies seem to exhibit sometimesonly a partial direct bone contact of a magnesium based alloy after acertain time if implantation. A fibrous tissue layer separates the newlygrown bone from the implant. Additionally, hydrogen gas formation andsometimes even gas bubbles seem to be present on the surface of theimplant and in the surrounding tissue after 6 to 12 weeks ofimplantation. Hydrogen gas evolution or release occurs during thebio-degradation process. The volume of evolved or released hydrogen gasis related to the dissolution of the magnesium. Without being restrictedto a theory it is believed that all of these problems are mainly oressentially due to a too fast initial degradation process of themagnesium implant in-vivo. The degradation rate of the magnesium basedalloys seems to be too fast, in particular at the beginning directlyafter implantation. More hydrogen gas is generated than can be readilyresorbed or absorbed by the surrounding tissue. This results in theformation of gas bubbles or gas pockets, for instance subcutaneous gasbubbles and/or gas bubbles in the soft-tissue, which could damage thesurrounding tissue. This is the major drawback of magnesium and actuallyhampers the broad application of magnesium based implants.

A recent approach bases on a magnesium based alloy having an adaptedcomposition and morphology. One specific alloy is designed. Thecomposition and the morphology are adapted or designed such thathydrogen gas evolution is avoided (see for instance N. Hort et al., ActaBiomaterialia, Volume 6, Issue 5, Pages 1714-1725, May 2010: “MagnesiumAlloys as Implant Materials—Principles of Property Design for Mg—REAlloys”).

On one hand the design of such an alloy is time-consuming and thereforeexpensive. On the other hand such a specific alloy possesses only onespecific degradation rate. However, in general the degradation rate isdependent on the place of implantation in the body or on the purpose ofthe implant. For instance, the degradation times of an implant acting asa fixture to hold together a bone long enough to allow natural healingto take place and of an implant embodied as a screw to fix a ligament toa cartilage can be different.

Accordingly, it is an object of the present invention to provide apreferably bio-degradable implant of advanced properties, for instanceof enhanced bio-compatibility and/or for providing improvedimplant-tissue-contact.

A bio-degradable implant should have a reduced degradation rate comparedto untreated implants. Particularly, the degradation rate, in particularthe initial degradation rate, should be reduced such that a gasaccumulation in the tissue is at least reduced or avoided.

In particular it should be possible to control or to adapt thedegradation rate or the bio-degradability of such an implant.

Preferably the ingrowth of human tissue and/or bone should be promotedby such an implant.

The fabrication of such an implant should be based on an easy and costreduced concept.

SUMMARY OF THE INVENTION

The inventive solution of the object is surprisingly achieved by each ofthe subject matter of the respective attached independent claims.

Advantageous and/or preferred embodiments or refinements are the subjectmatter of the respective attached dependent claims.

The concept of the present invention generally bases on applying acoating onto an implant of a bio-degradable material wherein the coatingis formed by an especially adapted plasma electrolytic oxidation (PEO),in particular having an especially adapted dispersed system. Such aPEO-coating, in particular in combination with a deposited orconstituted apatite, preferably hydroxyl-apatite, enhancesbio-compatibility and/or decreases the degradation rate or slows-downdegradation. The formation of a coating enables a flexible adaptation ofthe degradation time of such a bio-degradable implant. The evolution orrelease of hydrogen gas, in particular the initial evolution of hydrogengas, is decreased. Such a coating, in particular in combination with anapatite, preferably hydroxyl-apatite, also improves osseointegration.

Accordingly, the invention proposes a method for treating a surface ofa, preferably bio-degradable, metallic implant comprising the followingsteps:

providing a dispersed system comprising a colloid-dispersed apatite and

adding an apatite powder to the dispersed system or providing an apatitepowder in the dispersed system,

subjecting an implant, preferably a metallic implant, to the dispersedsystem such that a surface of the implant which is to be treated isimmersed in the dispersed system, preferably wherein the implantcomprises or is a magnesium based alloy,

applying an AC voltage difference between the implant as a firstelectrode and/or a second electrode positioned in the dispersed systemfor generating a plasma electrolytic oxidation on the immersed surfaceof the implant

so that the immersed surface is converted to an oxide film, inparticular of the magnesium based alloy, which is at least partiallycovered by apatites which are, in particular at least partially, formedor constituted by the apatite powder and preferably thecolloid-dispersed apatite.

The above mentioned method for treating a surface of a bio-degradablemetallic implant also can be called as a method for adapting or forcontrolling the bio-degradability of a bio-degradable metallic implantor as a method for enhancing or controlling the degradation resistanceof a bio-degradable metallic implant.

The invention also proposes an implant comprising a metal, preferably abiodegradable magnesium based alloy, having a treated surface wherein

the treated surface is at least partially converted to an oxide film byplasma electrolytic oxidation using a dispersed system comprising acolloid-dispersed apatite and an apatite powder and wherein

the converted surface is partially covered by apatites originating, inparticular at least, from the apatite powder and preferably thecolloid-dispersed apatite.

The colloid-dispersed apatite and the components of the apatite powderare deposited on the converted surface of the implant and/or at leastpartially form an apatite covering on the converted surface of theimplant. The converted surface of the implant can be completely coveredby the apatite covering. In dependence on the desired implant propertiesthe apatite covering can form island-like and/or coral-like structuresand/or clusters and/or a continuous or essentially continuous layer orcoating on the converted surface of the implant. The implant accordingto the invention is characterized by an adapted or controlled orcontrollable degradation or degradation rate.

A porous oxide film or layer is grown by the plasma electrolyticoxidation (PEO) process. By the PEO process, the metallic substrate isprovided as the first electrode, preferably as an anode, in an“electrolytic cell”. Its surface is converted into the correspondingmetal oxide under the applied electrical field. The oxide film consistsof crystalline phases, with a highly porous surface and with componentsderived from both the dispersed system and the implant as a substrate.It is provided a synthesis of ametal-oxide-apatite-nanocomposite-coating by in situ deposition. Theapatites are or the apatite is applied or deposited onto and/orconstituted on the surface of the implant when oxidizing the implantsurface. The present invention enables the formation of a coating ontoany type of shape of an implant.

The colloid-dispersed system also can be called dispersion. It is aliquid containing dispersed particles, in detail containing thecolloid-dispersed apatite and the apatite powder respectively itscomponents.

Since the colloid-dispersed apatite owns a size in the nm-order, thesize measurement in these dimensions is quite challenging. However, ingeneral the colloid-dispersed apatite is expected to be provided, inparticular at least partially, with an average size of about equal orless than 100 nm. The colloid-dispersed apatite generally has anelongated structure (for instance see FIG. 1 e). In one embodiment theaverage length is ranging up to 100 nm. The size measurement bases onSTEM (Scanning Transmission Electron Microscopy). It is emphasized thatthe size or the size distribution of the colloid-dispersed apatiteessentially also depends on particle agglomeration. Therefore, to getthe colloid-dispersed apatite in a non-agglomerated state, possibleagglomerated particles have to be separated or an agglomeration has tobe “destroyed”. Accordingly, a separation process or deagglomeration hasto be induced before the size measurement, for instance by means of anultrasonic device.

The combination of the colloid-dispersed apatite and the apatite powderis essential for the formation of apatite clusters or an apatitecovering on the converted implant surface. Without being restricted to atheory the following explanation is assumed:

The colloid-dispersed apatite represents small apatite particles, inparticular with respect to the average size of the apatite powder. Thecolloid-dispersed apatite seems or its components seem to be too smallfor the formation of an apatite covering. It seems to be more likelythat the colloid-dispersed apatite particles are destroyed in theintentionally generated plasma discharge of the PEO.

Since a powder generally owns a broad size distribution the apatitepowder contains also large apatite particles. The size distribution ofthe apatite powder depends on and/or can be adjusted by its fabricationprocess (as explained in the subsequent description). A possible apatitepowder distribution is provided with an average size ranging from 10 μmto 100 μm. The size measurement bases on LPS-analysis (Laser ParticleSpectrometer). This enables the formation of an apatite covering on theoxide film of the converted implant surface. However, surprisingly theexperimental results show that the application of the apatite powder inthe dispersed system only, results to a coating with a clearly reducedor even no apatite covering. It is believed large particles alone arenot able to stick on or to be deposited onto the oxide film of theconverted implant surface.

The colloid-dispersed apatite seems to act as a kind of bonding agent orsacrificial apatite which promotes the deposition and/or bonding oflarger sized apatite powder particles and/or the constitution of anapatite coating on the oxide film of the converted surface. The apatitepowder alone does not seem to contain a sufficient amount of smallapatite particles, even if the drying process and/or the milling processseem to be adjusted accordingly. In a further alternative and/orsupplementary assumption the particles of the apatite powder seem to benot in an appropriate state.

The combination of the colloid-dispersed apatite and the apatite powder,in particular each having the above shown respective possible sizedistribution, enables the formation of a quite uniform and/or continuousapatite or non-continuous apatite distribution and/or apatite coveringor layer.

The colloid-dispersed apatite is provided in a dispersed state. In onepreferred embodiment the colloid-dispersed apatite is provided orfabricated by means of precipitation process. The colloid-dispersedapatite is provided as a raw material, in particular directly orindirectly taken from the fabrication. With respect to the fabricationof the colloid-dispersed apatite it is referred to the patent EP 0 938449 B1. The content of this patent application is completelyincorporated by reference.

The fabrication of the colloid-dispersed apatite is only describedbriefly: The constituents forming apatite and/or apatite molecules areprovided dissolved or dispersed in a solution or suspension. Byprecipitation and in particular by a time-dependent agglomeration thecolloid-dispersed apatite is formed or constituted. Generally, such aprecipitated and preferably agglomerated colloid-dispersed apatite is acrystalline or nano-crystalline particle. For further fabricationdetails it is referred to the above stated incorporated patentapplication.

Said precipitated and/or precipitated and agglomerated colloid-dispersedapatite represents the above mentioned raw material. The solution orrather the dispersion of the colloid-dispersed apatite can be useddirectly in the present invention. The dispersion of thecolloid-dispersed apatite can be diluted to the required concentrationas well. Generally, the required colloid-dispersed apatite concentrationhas to be set for the dispersed system.

Also the apatite powder respectively its components are dispersed andnot dissolved in the dispersed system. The apatite powder can be addedto the dispersed system as being pulverized or as being part of anotherdispersed system. The powder is produced by drying the above mentionedfabricated raw material. By drying the dispersion respectively theprecipitated and preferably agglomerated colloid-dispersed apatite,apatite solid matter or a kind of apatite solid matter is constituted orformed. The apatite powder can be provided by drying, preferably byspray-drying, the precipitated and/or the precipitated and agglomeratedcolloid dispersed apatite only. Since for instance the spray-dryingresults already in a pulverized or powdery state. Accordingly, in thisvariant the apatite powder according to the invention is provided by adried material only.

In a further embodiment and in dependence on the drying process, by anoptional or obligatory subsequent milling process and/or pulverizingprocess the apatite powder according to the invention is made. Thepowder particle size distribution can be adjusted by the used millingand/or pulverizing process. Preferably the powder particle sizedistribution is fabricated to the above mentioned powder particle sizedistribution. Accordingly, in this embodiment the apatite powder isprovided by a dried and milled and/or pulverized material.

A large amount or high concentration of colloid-dispersed apatite seemsto be necessary to achieve the deposition and/or formation of theapatite covering on the converted surface. Preferably, thecolloid-dispersed apatite is provided in the dispersed system with ahigher concentration than the apatite powder. Preferably thecolloid-dispersed apatite is provided in the dispersed system with aconcentration of 0.01 mg/l to 300 g/l, preferably 10 mg/l to 200 g/l,most preferably 0.1 g/l to 100 g/l. In particular the apatite powder isprovided in the dispersed system with a concentration of 0.01 mg/l to200 g/l, preferably 10 mg/l to 100 g/l, most preferably 0.1 g/l to 50g/l.

The colloid-dispersed apatite and/or the apatite powder is respectivelyare at least one apatite selected from a group consisting ofhydroxyl-apatite, flour-apatite and carbonate-apatite. Hydroxyl-apatite(HA) is the preferred embodiment of an apatite. HA improvesosteoconduction. This enables a strong fixation of an implant insertedin a human body or in an animal body. It is assumed that an apatite, inparticular HA, additionally retards or inhibits degradation. Further, anapatite, in particular HA, increases the bio-compatibility of animplant. Furthermore, the application of an apatite, in particular HA,results in a direct cell contact of the implant with osteoblasts.

The notation of pure HA is as following: Ca₁₀(PO₄)₆(OH)₂. The HA can bea substituted HA, in particular a multi-substituted HA, as well.Examples of substitution are as following:

the Ca²⁺-sites of an apatite can be at least partially substituted byanother constituent. Possible examples for the Ca²⁺-constituent areSr²⁺, Cd²⁺, Mg²⁺, Ba²⁺, Pb²⁺, Cu²⁺, Zn²⁺, Na⁺, K⁺and/or Eu³⁺,

the OH⁻-sites of an apatite can be at least partially substituted byanother constituent. Possible examples for the OH⁻-constituent are F⁻,Cl⁻, Br⁻, I⁻, S²⁻, O²⁻ and/or CO₃ ²⁻ and/or

the PO₄ ³⁻-sites of an apatite can be at least partially substituted byanother constituent. Possible examples for the PO₄ ³⁻-constituent areSiO₄ ³⁻, AsO₄ ³⁻, SO₄ ³⁻, MnO₄ ³⁻, VO₄ ³⁻, CrO₄ ³⁻, CO₃ ²⁻ and/or HPO₄²⁻.

For instance a HA-Si-compound is a so-called Si-substitutedhydroxyl-apatite in which at least one PO₄ ³⁻ group is replaced by aSiO₄ ³⁻ group. Such a HA-Si-compound is characterized by an enhancedbio-compatibility.

The dispersed system can be based on any kind of liquid. In oneembodiment the dispersed system is provided as a water-based dispersion.Preferably the dispersion means are pure water or ion-exchanged water.The ph-value of the used water is less than or equal to 7.4. One examplerepresents sterile water for irrigation.

Since neither the used colloid-dispersed apatite nor the apatite poweris dissolved or comprises conductive particles, it is or can benecessary to provide conducting means in the dispersed system. Somepossible examples for providing conductivity in the dispersed systemrepresent dispersed metallic nano-particles and/or dissolvedelectrolytes. Conducting means also can be provided by an emulsifierwhich is required to provide a stable dispersed system. Also dissolvedmaterial, for instance of the immersed implant, can contribute to theconductivity in the dispersed system.

In a further embodiment of the present invention at least one additiveis added to or provided in the dispersed system. Dependent on itsproperty the additive is dissolved or dispersed in the dispersed system.Accordingly the additives are provided as electrolytes or as dispersedparticles.

In one embodiment the added dispersed particles are provided asnano-particles. Said nano-particles generally have a mean averagediameter of less than or equal to 100 nm, preferably less than or equalto 50 nm, most preferably less than or equal to 30 nm. Preferably thenano-particles, in particular the metallic nano-particles, are providedwith a concentration of less than or equal to 100 mg/l.

In one embodiment of the invention the additive contributes to theconductivity in the dispersed system. Generally, an additive is chosento be not harmful to the body but helpful for slow-down degradationand/or to avoid hydrogen gas release and/or accumulation.

One possible additive for the dispersed system is water glass which isadded to or provided in the dispersed system. Possible examples forwater glass are sodium water glass (Na₂SiO₃) and/or potassium waterglass. Water glass reduces degradation and is effective in bonemineralization. Further, water glass enhances or promotes adhesion ofthe additives and/or the colloid-dispersed apatite and/or the apatitepowder on the metallic surface. Furthermore, water glass promotesbonding between different minerals, added electrolytes and/orcolloid-dispersed apatite and/or the apatite powder. The water glass canbe provided in a liquid or as a liquid and therefore in a dissolvedstate. The water glass can be provided as a powder or in a solid stateas well. Particularly the water glass is provided in the dispersedsystem with a concentration of 0.01 g/l to 400 g/l, preferably 0.01 g/lup to 200 g/l and most preferably 0.01 g/l to 50 g/l. The mostlypreferred range is between 0.01 g/l to 15.0 g/l.

As an alternative or as a supplement at least one calcium containingcompound and/or at least one phosphate containing compound is added toor provided in the dispersed system. These compounds promote theformation of apatite on the converted implant surface and/or the bondingof apatite to the converted implant surface.

As a further alternative or supplement at least one metal and/or atleast one metal oxide and/or at least one metal hydroxide and/or atleast one metal phosphate containing compound is provided in thedispersed system. The compounds and/or the constituents of the compoundsare or can be embedded in the converted surface and/or deposited ontothe converted surface and/or contribute to the constitution of apatite.

The metal, the metal of the metal oxide, the metal of the metalhydroxide and/or the metal of the metal phosphate containing compound isat least one metal which selected from a group consisting of at leastone component of a material of the implant, sodium, potassium,magnesium, calcium, zinc, copper, silver, zirconium, aluminum, siliconand at least one component of the material of the implant.

With respect to the at least one component of the material of theimplant: If the implant metal comprises magnesium, the additive isprovided by magnesium. The metal additive is adapted to the substratematerial (representing the implant). A contamination can be avoided.

It is expected that calcium and calcium phosphate compounds retard orinhibit degradation, increase bio-compatibility and contribute to theformation of an apatite covering. Typical examples represent calciumdihydrogenphosphate, dicalcium phosphate, amorphous calcium phosphateand/or β-TCP (tri-calcium-phosphate).

Some chosen additives, in particular the metal oxides or oxides ingeneral, are believed to be a kind of scavenger. They are suitable tocatch the released or evolved hydrogen gas which originates fromdegradation of the magnesium implant. Accordingly, gas bubble formationin the tissue can be at least reduced or avoided. Hydrogen gas evolutionreduction can be such that the amount of hydrogen gas is resorbed orabsorbed by the surrounding tissue. For instance calcium represents acalcium source for the formation or bonding of apatite. Silver, zincand/or copper show an antibacterial effect.

Preferably the added metal oxide and/or the added metal hydroxide and/orthe added metal phosphate containing compound is provided in thedispersed system with a concentration of less or equal to 20 g/l butlarger than zero g/l. It is emphasized that above mentioned additivesare exemplary and not restricted to this enumeration. The abovementioned concentrations relate to the concentrations in the dispersedsystem which is ready to be used for the PEO coating.

In a further embodiment a gas is provided in the dispersed system. Thegas is for instance provided by a kind of bubbling. Particularly the gasis provided such to influence the PEO and/or to participate in the PEO.The gas comprises at least one type of gas selected from a groupconsisting of N₂, Ar, Kr and Xe. The mentioned noble gases are inparticular suitable to achieve an enhanced densification of theconverted layer.

The converted implant surface is uniformly covered with the oxide layer.Preferably the converted surface is continuously covered with the oxidelayer. The thickness of the oxide layer is adapted to the application ofthe implant. In general the oxide film has a thickness of 0.1 μm to 100μm, preferably 1 μm to 100 μm. A PEO converted surface according to oneembodiment can be characterized by an enhanced roughness in comparisonto a “simple” anodic oxidation process. Such a surface structure resultsin an implant surface of large specific surface area. For instance arough surface is particularly advantageous for the ingrowth of tissueand a strong fixation of an implant in a body.

As already stated in the preceding description the colloid-dispersedapatite and/or the apatite powder are applied onto the surface of theimplant when oxidizing the implant surface. A small fraction of apatiteor its constituents also can be embedded in the oxide layer. The mainfraction of the apatite is deposited onto the surface of the oxide layerand forms the continuous or non-continuous layer.

There exists no sharp interface between the oxide layer and thedeposited or bonded apatite particle layer. The apatite particleconcentration in the converted implant surface should be decreasing,preferably continuously decreasing, with increasing depth.

The apatite covering forms a coral-like structure on the convertedsurface. In dependence on the application of the implant the apatitecovering can be provided as a partially covering on the convertedimplant surface or as a complete covering on the converted implantsurface. An average thickness of an apatite covering should be in therange of 1 nm to 1000 nm. The apatite covering are provided by means ofmicro-arcs in the PEO process, for instance by implantation and/ordeposition and/or agglomeration and/or constitution of the apatitepowder and preferably also the colloid-dispersed apatite.

In one embodiment the apatite covering forms an island-like structure onthe converted surface wherein the islands have an average area size ofless than 3000 nm. The islands are surrounded by the oxide layer. Someislands also can be connected to each other. The island-like structurerepresents a non-continuous layer or film on the oxide film.Accordingly, the constituents Mg, MgO and the constituents of an apatiteare directly “visible” respectively detectable on the surface.

The controlling of the covering amount of the apatite can be used toadjust or control its “effect”. For instance the free or visible area ofthe oxide film of the converted surface can be adjusted. Both thedegradation rate (corresponding to the bio-degradability of the implant)and the osteoconduction can be adjusted accordingly.

One parameter for the degradation rate represents the amount of hydrogengas release or evolution. An implant according to the invention,preferably based on W4 magnesium alloy, is characterized by a hydrogenevolution rate of less than or equal to 1 ml/cm⁻² day⁻¹. It isemphasized that the hydrogen gas evolution represents only onedegradation process.

The degradation rate is determined by Electrochemical ImpedanceSpectroscopy (EIS). For example, one type of coated implant composed ofW4-alloy is characterized by a degradation rate in terms of corrosionrate of less than or equal to 100 mpy, preferably of less than or equalto 60 mpy, most preferably of less than or equal to 20 mpy (mils peryear). The listed degradation rate represents the initial degradationrate.

The AC voltage or alternating voltage is applied to the first electrodeand/or the second electrode. The AC voltage is provided with a frequencyof 0.01 Hz to 1200 Hz.

In a preferred embodiment the AC voltage is provided as an asymmetric ACvoltage. The asymmetric AC voltage difference or asymmetric AC voltagerepresents an unbalanced AC voltage. This is an alternating voltage withdifferent amplitudes to the negative and the positive components. It isemphasized that a pulsed DC voltage can be also interpreted as the ACvoltage. The negative component is provided with amplitude ranging from−1200 V to −0.1 V. Preferably, the negative component is provided withamplitude ranging from −350 V to −0.1 V. In one embodiment, the negativecomponent is provided with amplitude below −180 V or ranging from −350 Vto −180 V. The positive component is provided with amplitude rangingfrom 0.1 V to 4800 V. Preferably, the positive component is providedwith amplitude ranging from 0.1 V to 1400 V. In one embodiment, thepositive component is provided with amplitude above +250 V or rangingfrom +250 V to 1400 V. In particular the quotient of the positiveamplitude divided by the negative amplitude needs to be adjusted. Theabsolute value of the quotient ranges from larger 1 to 4.

In another embodiment the AC voltage is provided as a symmetric ACvoltage. The negative component of the AC voltage is provided withamplitude ranging from −2400 V to −0.1 V. Preferably, the negativecomponent is provided with amplitude ranging from −1200 V to −0.1 V. Thepositive component of the AC voltage is provided with amplitude rangingfrom +0.1 V to +2400 V. Preferably, the positive component is providedwith amplitude ranging from 0.1 V to 1200 V.

A combination of both an asymmetric and a symmetric AC voltage is alsopossible. Such a voltage distribution is for instance suitable for astep-by-step-process or a multi-step-process for the fabrication of onecoating. In a first step an asymmetric voltage or a symmetric voltage isapplied to form the coating. In a further or second step, in particularafter an interruption, the formation of the coating is continued by theapplication of a symmetric voltage or an asymmetric voltagerespectively.

The voltage difference is provided with a magnitude which is sufficientfor carrying out PEO. It is established an electric potential differenceunder plasma electrolytic conditions. The voltage is above a breakdownvoltage of the oxide film growing on the surface of the implant.Preferably the maximum of the AC voltage difference is provided in therange of 0.1 V to 4800 V. Most preferably the maximum of the AC voltagedifference is provided in the range of 100 V to 1400 V. In dependence onthe conductivity of the dispersed system, the applied voltage differenceresults to a current density of 0.00001 to 500 A/dm², preferably of0.00001 to 100 A/dm². Preferably, the applied voltage or voltagedistribution is essentially constant or unchanged and the currentdensity is adjusted during the PEO process.

A deposition rate in the range of 0.01 μm/s to 1 μm/s is achieved.Accordingly, with respect to the advantageous thickness of the oxidelayer and/or the apatite islands a deposition time in the range of 1 sto 1500 s, preferred 1 s to 500 s, most preferred 20 s to 350 s, isachievable.

To enable a stable dispersion, the colloid-dispersed system is providedwith a temperature of −20° C. to +150° C., preferably −20° C. to +100°C., most preferably between 0° C. to 75° C. The colloid-dispersed systemis circulated with a circulation rate of 0 to 5000 liter/min, preferably0.01 to 500 liter/min. This is for instance achieved by a mixer ormixing means or stirring means. As an optional supplement an emulsifyingagent or emulsifier is provided in the dispersed system, in particularto avoid or to reduce an agglomeration of dispersed particles. A typicalvolume of the colloid-dispersed system is in the order of 0.001 liter to500 liter, preferably 0.1 liter to 500 liter, most preferably 3 to 20liter. Such volumes support an improved electrical field distribution inthe dispersed system.

The implant according to the invention could be used in the field oftraumatology, orthopaedic, spinal surgery and/or maxillofacial surgery.By means of a preferably surgical operation the implant is at leastpartially inserted or positioned in a human body and/or an animal body.The implant could be any kind of implant, preferably a surgical implant,which should not be removed in a further surgical operation. The implantcould act as a preferably bone substitute as well.

Exemplary embodiments of such an implant according to the invention areplates, screws, nails, pins and/or at least partially internal fixationsystems, rings, wires, clamps, blocks, cylinders and/or anchor items. Itis emphasized that these applications are exemplary and not restrictedto this enumeration.

The implant consists of metal or comprises metal. According to a firstembodiment the implant is provided by a metal or by a metal alloy.According to a second embodiment the implant is provided by a compositeor a composite material comprising a metal or a metal alloy. Such acomposite or composite material contains metal or a metal alloy with anamount of at least 70 weight %.

The surface converted implants according to the invention base in apreferred embodiment on bio-compatible materials, preferably beingbio-degradable. The material of a bio-degradable implant is magnesium ora magnesium-based alloy.

The magnesium-based alloy contains at least 50 weight-% of magnesium,preferably at least 80 weight-% of magnesium, most preferably at least90 weight-% of magnesium. An actually used alloy is the W4 Magnesiumalloy (96% Magnesium, 4% Yttrium). Magnesium alloys were developed fororthopaedic applications. They have a Young modulus very close to thatof natural bone and show excellent biocompatibility andbio-resorbability. The magnesium-based alloy is provided as a machinedmaterial, pressure casted material and/or die casted material. It isexpected that the present invention is also suitable for furthermaterials, in particular for metals preferably being non-bio-degradable,for instance to enhance bio-compatibility. In this embodiment theimplant comprises at least one material selected from the groupconsisting of titanium, titanium alloys, chromium alloys, cobalt alloysand stainless steel. An alloy comprises at least 50 weight-% of thenamed main element. It is emphasized that above mentioned alloys and/orthe fabrication methods are exemplary and not restricted to thisenumeration.

In particular the implant according to the invention is producible,preferably is produced, with the method according to the invention. Theimplant comprises a surface composed of an oxide film which is partiallyor completely covered with an apatite covering.

The invention is explained subsequently in more detail on the basis ofpreferred embodiments and with reference to the appended figures. Thefeatures of the different embodiments are able to be combined with oneanother. Identical reference numerals in the figures denote identical orsimilar parts.

BRIEF DESCRIPTION OF THE DRAWINGS

It is shown in

FIG. 1 a schematically an apparatus for the fabrication of a coatingaccording to the invention,

FIG. 1 b schematically a first embodiment of an asymmetric AC voltagedistribution,

FIG. 1 c schematically a second embodiment of a symmetric AC voltagedistribution,

FIG. 1 d schematically a third embodiment of an asymmetric AC voltagedistribution combined with a symmetric AC voltage distribution and

FIG. 1 e shows a STEM image of nanoHA,

FIGS. 2 a to 5 b show results of a HA-MgO coating according to theinvention which is applied onto a srew which is based on a magnesiumalloy.

In detail, it is shown in

FIGS. 2 a to 2 c: images of the HA coating according to the inventionusing common photography (a), SEM in topography contrast mode (b) and aschematic cross sectional view of the converted surface (c),

FIGS. 3 a-b: an SEM image of the HA coating without nano-HA in chemicalcontrast mode (a), an EDX spectra of the bright region indicated by thetip of the arrow (b),

FIGS. 4 a-b: an SEM image of the HA coating with nano-HA in chemicalcontrast mode (a), an EDX spectra of the bright region indicated by thetip of the arrow (b),

FIGS. 5 a-b: the experimental results of immersion tests (a) and ofelectrochemical impedance spectroscopy (b) for an uncoated sample, asample coated with nano-HA and sample coated without nano-HA.

Subsequently, preferred but exemplary embodiments of the invention aredescribed in more detail with regard to the figures.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 illustrates an apparatus for the fabrication of a coatingaccording to the invention. The subsequent detailed description isdirected to an implant. For instance for the coating of bio-degradablesurgical implants the present innovative technique based on Plasmaelectrolytic oxidation (PEO) has been developed. PEO is anelectrochemical surface treatment process for generating oxide coatingson metals.

As a pulsed alternating current, with a high voltage, is passed throughthe dispersed system 4 or the electrolyte bath 4, a controlled plasmadischarge is formed and sparks are generated on the substrate surface.This plasma discharge converts the surface of the metal into an oxidecoating. The coating is in fact a chemical conversion of the substrateand grows both inwards and outwards from the original metal surface.Because it is a conversion coating, rather than a deposited coating(such as a coating formed by plasma spraying), it has excellent adhesionto the substrate metal.

The dispersed system 4 is provided in a bath 5. An implant 20 as a firstelectrode 1 is provided in the dispersed system 4. In the illustratedembodiment the implant 20 is completely immersed in the liquid 4respectively the dispersed system 4. A second electrode 2 is provided asa cup also immersed or provided in the colloid-dispersed system 4. Thesecond electrode 2 surrounds the first electrode 1.

The temperature of the dispersed system 4 is maintained or controlled bya heat exchanger 6 and/or a pumping system 7 and/or means for mixing 8.A circulation and/or mixing of the dispersed system 4 are achieved bythe means for mixing 8. The means for mixing 8 are for instance providedby an acoustic hydrodynamic generator. As a possible and shownsupplement a gas supply 9, for instance for air, can be also provided tothe means for mixing 8. The circulation of the liquid can avoid orreduce an agglomeration of dispersed particles and/or can induceseparation of agglomerated particles contained in the dispersed system4.

In a further non-shown embodiment the second electrode 2 is provided bythe bath 5 or the container 5 itself. This is for instance suitable fora container 5 which is provided by a conductive material. In such anembodiment the bath 5 and the second electrode 2 are provided asone-piece. In a preferred embodiment the first electrode 1 isapproximately positioned in the center of the second electrode 2 inorder to achieve an essentially uniform electrical field distribution.

The AC voltage is provided by the power supply 10 (see FIG. 1 a). Theapplication of an asymmetric pulsed AC voltage results in a densecoating. The positive part of the pulse enables the growing of theconverted surface. At the beginning of the oxide layer growing processthe converted surface is characterized by a dense structure. Withincreasing oxide layer coating thickness the coating is getting more andmore porous. The particles of the coating are getting more and moreloosen. These loosen particles are removed in the negative part of thepulse. Accordingly, the negative part of the pulse is a so-calledetching part. An asymmetric AC voltage is a voltage with differentamplitudes to the positive and negative components. In particular thequotient of the positive amplitude divided by the negative amplitudeneeds to be adjusted. The absolute value of the quotient ranges from >1to 4. For illustration purposes FIG. 1 b schematically shows anasymmetric AC voltage distribution for amplitudes U1 of +200 V and −50V.These voltages are for instance applied to the implant 20 as the firstelectrode 1 (see FIG. 1 a). In this embodiment the voltage of the secondelectrode 2 is for instance on ground potential. The shape isillustrated as being approximately rectangular-shaped. The shape canalso be, in particular partially, a kind of a sinus or a sinus.

For some applications also a symmetric AC voltage distribution issuitable. One exemplary application is the obtaining of a coating with avery high surface roughness for improved implant-bone bonding. Forillustration purposes FIG. 1 c schematically shows a symmetric ACvoltage distribution for amplitudes U1 of −200 V and +200V.

FIG. 1 d shows a combination of both an asymmetric and a symmetric ACvoltage. The shown voltages correspond to the voltages shown in FIGS. 1b and 1 c. Only the period of the symmetric voltage is exemplaryreduced. Such a voltage distribution is for instance suitable for amulti-step-process for the fabrication of one coating. In a first stepan asymmetric voltage is applied to form a coating having a quite densestructure. In a second step, in particular after a break, the formationof the coating is continued by a symmetric voltage to obtain a surfacehaving an enhanced surface roughness.

FIG. 1 e shows a STEM image of colloid-dispersed apatite for theembodiment of HA. This colloid-dispersed apatite is also named asnanoHA. The shown nanoHA represents one embodiment for using in thepresent invention. As can be seen, the nanoHA has an elongatedstructure. The shown nanoHA is partially in an agglomerated state andpartially in a non-agglomerated state. The size distribution of thenanoHA essentially depends on time. The nanoHA is present asnon-agglomerated particles 30, as agglomerated particles or clusters ofsmall size 31 and as agglomerated particles or clusters of larger size32. The average length of non-agglomerated nanoHA is ranging up to 100nm. The present agglomerated and the non-agglomerated nanoHA representsraw material.

The FIGS. 2 a to 5 b show experimental results of a HA-MgO coatingaccording to the invention. Coating experiments were performed on diecasted W4 magnesium interference screws (8.2×25 mm). Pressure casted andmachined discs (18 mm, thickness 3 mm) of the same material were usedfor electrochemical impedance spectroscopy (see FIG. 5 b) and for theimmersion tests (see FIG. 5 a).

First, FIG. 2 a shows an image of the HA coating according to theinvention using common photography. As an example a screw having acoating according to the invention is shown. The coating surfacetopography was investigated by stereo scanning electron microscopy (SEM)in topography contrast mode (FIGS. 2 b: topographical characterizationaccording to ISO/TS 10993-19:2006). The images show a uniform andhomogeneous coating of the surface with HA.

For illustration purposes FIG. 2 c schematically shows a convertedsurface in a cross sectional view. The converted surface is continuouslycovered with the oxide layer and in this example only partially coveredwith HA. In this example the oxide film is characterized by hills and/orplateaus and/or craters separated by grooves and/or channels and/orridges. However, the oxide film can be also flat. Particles of thedispersed system are also completely or partially included or embeddedin the HA coating. Preferably the HA coating is formed by or built as acoral-like structure. As one example water glass and/or its constituentsare included or embedded. On top of the oxide layer in this example akind of apatite islands are developed forming a non-continuous layer ofapatites. The islands can be formed on the plateaus and in the grooves.

FIGS. 3 a to 4 b show the results of a physico-chemical characterization(according to ISO/TS 10993-19:2006). In these figures thecolloid-dispersed apatite is called as nanoHA. In detail FIGS. 3 a-bshow an SEM image of the HA coating in chemical contrast mode without oronly a low amount of nano-HA (3 a) and an EDX spectrum of the brightregion indicated by the tip of the arrow (3 b). FIGS. 4 a-b showcorresponding figures for the HA coating according to the invention withnano-HA.

The SEM image in chemical contrast mode clearly shows that there is noapatite or only a low amount of apatite or at least no detectableapatite on the surface of the sample which was treated in a dispersedsystem with an HA powder only but without nanoHA (see FIG. 3 a). Theapplied concentrations in the composition correspond to theconcentrations as mentioned below for the coating according to theinvention (see FIGS. 4 a and 4 b) but without nanoHA. It is a net-likestructure. The corresponding EDX spectrum confirms that there seems tobe no or only few amounts of the elements calcium and phosphor, whichare the main constituent elements of an apatite, on the PEO-formed oxidefilm of the converted surface. The oxide film is presented by theelements magnesium and oxygen.

This is in strong contrast to FIGS. 4 a and 4 b showing the results fora coating according to the invention. The SEM image in chemical contrastmode clearly shows the presence of a covering on the oxide film of theconverted surface. This covering is provided by a coral-like structureor layer (see FIG. 4 a). This covering can be also described as a kindof solidified foam. It is assumed that this coral-like structure isbuilt or formed by HA or represents a partial or complete HA covering.The coral-like structure is related to HA crystals bonded together onthe coating surface. The corresponding EDX spectrum confirms thisassumption (see FIG. 4 b). The elements calcium and phosphor being themain constituent elements of an apatite are present on the PEO-formedoxide film of the converted surface. Also the element silicon being oneconstituent of water glass is present in the spectrum. Accordingly,Ca—P—Si containing particles are found. The oxide film is presented bythe elements magnesium and oxygen. Generally, the apatite or thecoral-like structure owns an essentially elongated structure, forinstance a cylindrical-like or rod-like structure. The presence ofnanoHA in the dispersed system seems to be necessary for the formationof HA on the converted surface and/or for the deposition of HA onto theconverted surface and/or the bonding of HA to the converted surface.

The applied concentration of the HA powder is 1.4 g/l. The appliedconcentration of the nanoHA is 1.6 g/l. Colloid-dispersed apatiteparticles with a particle size of about 15 nm to 60 nm and an apatitepowder with a size distribution of 10 μm to 100 μm are very suitable.Additionally, the used dispersed system contains a concentration of 1.1g/l water glass.

The purpose of an apatite-coating is the adaptation and/or theretardation of degradation, in particular the initial degradation. Theinitial degradation represents the occurring bio-degradation of abio-degradable implant immediately or directly after implantation.

To illustrate the benefits of the present invention FIGS. 5 a and 5 bshow the experimental results of immersion tests (a) and ofelectrochemical impedance spectroscopy (b). Also in these figures thecolloid-dispersed apatite are called as nanoHA. The results are shownfor an uncoated magnesium W4 sample, a magnesium W4 sample coatedwithout nano-HA and a magnesium W4 sample having a coating according tothe invention in which the coating is formed or established both by thenanoHA and by the HA powder.

FIG. 5 a shows the entire acquired hydrogen volume which was evolvedfrom the sample respectively produced in the sample-solution-interactionas a function of the immersion time. The hydrogen gas evolutionmeasurement of magnesium is performed according to DIN 38 414. Asexpected the uncoated sample shows the highest hydrogen gas evolutionbecause the magnesium is completely exposed to the test solution.

The degradation of the sample which is coated without the nanoHA isalready reduced in comparison to the uncoated sample. This enhanceddegradation resistance essentially origins from the PEO-formed oxidelayer acting as a protection layer. The protecting oxide layer isgradually degraded by the test solution. Accordingly, the degradationincreases with increasing immersion time.

The inventors surprisingly discovered that the degradation resistancecan be tremendously enhanced by the combination of nanoHA and HA powderin the dispersed system. During the measured time spectrum essentiallyno hydrogen gas was evolved or formed respectively detected. This resultproves the efficacy of the combination of nanoHA and HA powder in thedispersed system. It is expected that the constituted apatite coveringor layer and the oxide coating will be gradually degraded in the end bythe test solution also. After a particular time interval the sample oran implant inserted in a body will start to degrade as wanted.Accordingly, in a larger time scale this will result to an appearing andraising hydrogen gas evolution with increasing time. By controlling theapatite cover amount and/or the thickness of the oxide film and/or theporosity of the apatite coating and/or the porosity of the oxide layerthe degradation characteristics of a bio-degradable implant based onmagnesium can be adapted to the desired or required behavior, forinstance the implant stability as a function of time.

FIG. 5 b shows the results of Electrochemical Impedance Spectroscopy(EIS) measurements (according to ASTM G-106). In EIS a corroding metalcould be modelized as an electrochemical system consisting of adouble-layer capacitance (C_(d1)), a solution resistance and a chargetransfer resistance (generally assimilated with the polarizationresistance, R_(p)). Such a system can be studied by using an AC signalthat can provide more information than a DC polarization. Thus, applyinga 5 mV sinusoidal potential through a potentiostatic circuit, thepotential-current response plots provide the impedance values. Theimpedance diagrams are recorded at the initial moment of time (t=0 h)immediately after the stabilization of the steady-state potential (about5 to 20 min after immersion).

The Nyquist plots of the magnesium alloy at an open circuit exhibit twocapacitive loops, one for high and intermediate frequencies and theother, the smaller one, for low frequencies. The first capacitive loopis attributed to the charge-transfer process. Thus, for the frequencieshigher than 1 Hz, a resistor R_(p) and a capacitor C_(d1) in parallelcan model the electrode/electrolyte interface. In some cases the secondsmall capacitive loop is generally attributed to the mass transfer inthe solid phase, which consists of the oxide/hydroxide layers.

The behavior of uncoated W4 in solutions imitating body's environments(0.9% NaCl solution stabilized with NaOH) was studied by electrochemicalimpedance spectroscopy (EIS). The purpose of this experiment was tocompare the different composition in terms of degradation rate. Thecoating duration was the same for all compositions: 150 sec. During theexperimental procedure 0.9% NaCl solution at body temperatures as wellas an external pH control were used. The parameters were adjusted asfollow: temperature of the solution—36.5-38.5° C., pH—7.35-7.45, flowrate of the solution between the reactor (500 ml) and theelectrochemical cell (500 ml)—100 ml/min, speed of circulation of thesolution inside of the electrochemical cell—300 ml/min. Measurementswere taken using a potentiostat PARSTAT 2263 device (EG&G PrincetonApplied Research) linked to a PC. Actually, the impedance diagrams wererecorded exemplary at the initial time (t=0 h). The degradation rate ateach time point can be deduced from the impedance diagram.

FIG. 5 b shows the degradation rate in terms of corrosion rate for theinitial time and therefore the initial degradation rate. The degradationrates of the two with apatite coated samples are all inferior to thedegradation rate of the uncoated sample. Consequently the two formedcoatings have a beneficial effect on the Mg-screws degradation.

However, the coated sample in which the coating was formed by bothnanoHA and the HA powder shows a clearly reduced degradation rate bothwith respect to the uncoated sample and the coated sample without usingnanoHA. The degradation rate, in particular the initial degradation rateis less than or equal to 20 mpy (mils per year).

Summarizing, it was shown that an HA-MgO coating according to theinvention shows improved properties in terms of reduced hydrogen gasevolution, in particular reduced initial hydrogen gas evolution, anddegradation resistance.

It will be understood that the invention may be embodied in otherspecific forms without departing from the spirit or centralcharacteristics thereof. The present examples and embodiments,therefore, are to be considered in all respects as illustrative and notrestrictive, and the invention is not to be limited to the details givenherein. Accordingly, features of the above described specificembodiments can be combined with one another. Further, featuresdescribed in the summary of the invention can be combined with oneanother. Furthermore, features of the above described specificembodiments and features described in the summary of the invention canbe combined with one another.

1. A method for treating a surface of a preferably bio-degradablemetallic implant comprising the following steps: providing a dispersedsystem comprising a colloid-dispersed apatite and adding an apatitepowder to the dispersed system, subjecting an implant to the dispersedsystem such that a surface of the implant which is to be treated isimmersed in the dispersed system, preferably wherein the implantcomprises a magnesium based alloy, applying an AC voltage differencebetween the implant as a first electrode and a second electrodepositioned in the dispersed system for generating a plasma electrolyticoxidation on the immersed surface of the implant so that the immersedsurface is converted to an oxide film which is at least partiallycovered by apatites formed at least by the colloid-dispersed apatite andthe apatite powder.
 2. The method of claim 1, wherein thecolloid-dispersed apatite is provided in the dispersed system with ahigher concentration than the apatite powder.
 3. The method of claim 1,wherein the apatite powder is provided in the dispersed system with aconcentration of about 0.01 mg/l to about 200 g/l.
 4. The method ofclaim 1, wherein the colloid-dispersed apatite is provided in thedispersed system with a concentration of about 0.01 mg/l to about 300g/l.
 5. The method of claim 1, wherein the colloid-dispersed apatite isprovided by precipitation.
 6. The method of claim 1, wherein the apatitepowder is provided by drying, in particular by spray-drying,precipitated colloid-dispersed apatite.
 7. The method of claim 1,wherein the apatite powder is provided by drying and by milling and/orby pulverizing precipitated colloid-dispersed apatite.
 8. The method ofclaim 1, wherein the colloid-dispersed apatite and/or the apatite powdercomprises hydroxyl-apatite and/or substituted hydroxyl-apatite.
 9. Themethod of claim 1, wherein water glass is added to the dispersed system.10. The method of claim 9, wherein the water glass is provided in thedispersed system with a concentration of about 0.01 g/l to about 400g/l.
 11. The method of claim 1, wherein at least one calcium containingcompound and/or at least one phosphate containing compound is added tothe dispersed system.
 12. The method of claim 1, wherein at least onemetal and/or at least one metal oxide and/or at least one metalhydroxide and/or at least one metal phosphate containing compound isadded to the dispersed system.
 13. The method of claim 12, wherein themetal, the metal of the metal oxide, the metal of the metal hydroxideand/or the metal of the metal phosphate containing compound is at leastone metal selected from a group consisting of sodium, potassium,magnesium, calcium, zinc, copper, silver, zirconium, aluminum, siliconand at least one constituent of a material of the implant.
 14. Themethod of claim 1, wherein the metal is provided in the dispersed systemwith a concentration of less than or equal to about 100 mg/l and/or themetal oxide and/or the metal hydroxide and/or the metal phosphatecontaining compound is provided in the dispersed system with aconcentration of less than or equal to about 20 g/l.
 15. An implantproduced according to claim
 1. 16. An implant comprising a metal,preferably a biodegradable magnesium based alloy, having a treatedsurface wherein the treated surface is at least partially converted toan oxide film by plasma electrolytic oxidation using a dispersed systemcomprising a colloid-dispersed apatite and an apatite powder and whereinthe converted surface is partially covered by apatite originating atleast from the colloid-dispersed apatite and the apatite powder.
 17. Theimplant of claim 16, wherein the colloid-dispersed apatite and/or theapatite powder comprises hydroxyl-apatite and/or substitutedhydroxyl-apatite.
 18. The implant of claim 16, wherein at least onemetal and/or at least one metal oxide and/or at least one metalhydroxide and/or at least one metal phosphate containing compound is atleast partially deposited onto the converted surface and/or embedded inconverted surface.
 19. The implant of claim 16, wherein the metal, themetal of the metal oxide, the metal of the metal hydroxide and/or themetal of the metal phosphate containing compound is at least one metalselected from the group consisting of: sodium, potassium, magnesium,calcium, zinc, copper, silver, zirconium, aluminum, and silicon and atleast one constituent of a material of the implant.
 20. The implant ofclaim 16 characterized by a controlled degradation.
 21. The implant ofclaim 16 characterized by a hydrogen gas evolution rate of less than orequal to about 1 ml/cm⁻² day and/or a degradation rate of less than orequal to about 100 mpy.